| 1. |
- Lin, Jake, et al.
(författare)
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Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we observe increased monocyte and decreased B cell proportions 9-12 months prior to autoantibody positivity, especially in children who developed antibodies against insulin first. Lastly, we show that control children present transcriptional signatures consistent with robust immune responses to enterovirus infection, whereas children who later developed islet autoimmunity do not. These findings highlight distinct immune-related transcriptomic differences between case and control children prior to case progression to islet autoimmunity and uncover deficient antiviral response in children who later develop islet autoimmunity.
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| 2. |
- Mårild, Karl, et al.
(författare)
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Celiac Disease and Anorexia Nervosa : A Nationwide Study
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 139:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Previous research suggests an association of celiac disease (CD) with anorexia nervosa (AN), but data are mostly limited to case reports. We aimed to determine whether CD is associated with the diagnosis of AN.METHODS: Register-based cohort and case-control study including women with CD (n = 17 959) and sex- and age-matched population-based controls (n = 89 379). CD (vinous atrophy) was identified through the histopathology records of Sweden's 28 pathology departments. Inpatient and hospital-based outpatient records were used to identify AN. hazard ratios for incident AN diagnosis were estimated by using stratified Cox regression with CD diagnosis as a time-dependent exposure variable. In the secondary analyses, we used conditional logistic regression to estimate odds ratios for being diagnosed with AN before CD.RESULTS: Median age of CD diagnosis was 28 years. During 1 174 401 person-years of follow-up, 54 patients with CD were diagnosed with AN (27/100 000 person-years) compared with 180 matched controls (18/100 000 person-years). The hazard ratio for later AN was 1.46 (95 A, confidence interval [Cl], 1.08-1.98) and 1.31 beyond the first year after CD diagnosis (95% Cl, 0.95-1.81). A previous AN diagnosis was also associated with CD (odds ratio, 2.18; 95% Cl, 1.45-3.29). Estimates remained largely unchanged when adjusted for socioeconomic characteristics and type 1 diabetes.CONCLUSIONS: The bidirectional association between AN diagnosis and CD warrants attention in the initial assessment and follow-up of these conditions because underdiagnosis and misdiagnosis of these disorders likely cause protracted and unnecessary morbidity.
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